SV2A expression and 18F-FDG PET in a diet-induced type 2 diabetes mouse model

Introduction: Type 2 diabetes mellitus (T2DM) is associated with cognitive impairment. Synaptic vesicle protein 2A (SV2A) is a synaptic biomarker that correlates highly with cognitive impairment. The objective of this study is to investigate the connection between SV2A expression and TD2M in a Western diet-induced T2DM model.

Methods: T2DM was established by feeding a Western diet to apolipoprotein E-deficient (ApoE-/-) mice with the C57BL/6J (B6) background (B6-ApoE-/-). Serum glucose, total cholesterol (TC), triglycerides (Tg), and brain 18F-FDG uptake by PET imaging were compared between the Western diet and the chow diet. SV2A expression in the cortex and the hippocampus of B6-ApoE-/- mice fed Western diet or chow diet was evaluated at 12 weeks by immunofluorescence staining and western blot analysis.

Results: Compared with chow diet, plasma glucose, total cholesterol, and triglycerides levels were significantly increased in B6-ApoE-/- mice after 12 weeks of Western diet. The standardized uptake value (SUV) of 18F-FDG was also significantly increased in whole brain (p=0.018) of B6-ApoE-/- mice fed the Western diet. Both immunofluorescence staining and western blot analysis showed that SV2A expression in the cortex and hippocampus was significantly lower in the Western diet group than chow diet group.

Conclusions: Diabetic mice exhibited significantly increased glucose metabolism and decreased SV2A expression in the brain. SV2A is a potential marker for evaluating cognitive impairment in diabetes.

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